#471 Iron Deficiency Anemia with Dr. Tom DeLoughery

Summary

The Curbsiders Internal Medicine Podcast

Episode #471: Iron Deficiency Anemia with Dr. Tom DeLoughery

Date: February 17, 2025
Host: Dr. Matthew Frank Watto, Dr. Paul Nelson Williams, Dr. Sai Achi
Guest: Dr. Tom DeLoughery, Hematologist, Oregon Health & Science University

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Episode Overview

This episode dives deep into the diagnosis and management of iron deficiency anemia, a condition common in internal medicine but rife with diagnostic and therapeutic nuances. Returning guest and hematology educator Dr. Tom DeLoughery brings a blend of evidence-based pearls and practical insights, exploring everything from interpreting CBCs to choosing and dosing oral and IV iron. Listeners will gain updated guidance for recognizing true iron deficiency, setting appropriate ferritin cutoffs, optimizing iron replacement strategies (including patient counseling and dietary myths), and knowing when to escalate care. The discussion is engaging, occasionally irreverent, and packed with clinical "aha!" moments for learners at all levels.

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Key Discussion Points & Insights

1. Approaching Anemia: Diagnostic Framework

[09:36]

• Initial approach: Assess for bleeding, prior anemia, family history, and GI/celiac symptoms.

• Begin with a basic CBC review. Use a focused workup guided by MCV and clinical clues.

  “When I see somebody’s anemic and labs come back anemic...have you been bleeding?...stomach upset, diarrhea—trying to tease out celiac disease.”
  — Dr. DeLoughery [09:36]

Dr. DeLoughery’s Quick CBC Review

[13:42]

• Focus on hemoglobin, MCV, and red cell count.

• Avoid over-interpreting indices like RDW or MCHC, as they're rarely helpful diagnostically.

  "For a CBC, I’m fairly limited...if they adopted my view on CBCs, we’d save so many trees and paper.”
  — Dr. DeLoughery [14:27]

Parlor Trick: Distinguishing Thalassemia vs Iron Deficiency

[15:49]

• MCV ÷ RBC (in millions):
  • <13: Thalassemia likely
  • >13: Iron deficiency more likely
• “In thalassemia you make a lot of little red cells. In iron deficiency, you don’t make a lot of little red cells.”
  — [15:49]

2. Iron Studies: What Really Matters

[19:21 & 21:04]

• Ferritin is the single most reliable test for iron deficiency.

• Transferrin saturation and TIBC are less useful, especially in inflammation or elderly patients—can be misleading.

  “The one test that is most predictive is the serum ferritin. So I just tend to go with that.”
  — Dr. DeLoughery [20:49]

3. Ferritin Cutoffs—A Paradigm Shift

[21:04]

• Classic lower limits (e.g., 15–30 ng/mL) are too low; they reflect iron-deficient reference populations.

• Modern cutoff:

  • Under 30 is highly sensitive/specific for negative iron stores
  • Under 50 is a better cutoff for symptomatic/fatigued patients or for normalization of absorption.

• Higher cutoffs (e.g., 75–100+) may be needed for conditions like restless legs syndrome and alopecia.

  “We need to move away from population-based data to more physiologic data...For a healthy person, probably 30...What's interesting though is there's two studies that show...for feeling better is 50 with oral iron.”
  — Dr. DeLoughery [21:04]

Inflammation Pitfall

• Ferritin is an acute phase reactant but in pure iron deficiency, rarely rises above 100—even in inflamed states.

  “If somebody’s ferritin is 600, they are not iron deficient, because you need iron to make the ferritin protein.”
  — [23:05]

Clinical Pearl

[27:23]

• Fatigue/alopecia/restless legs may require ferritin >75–100; “...give [such patients] iron, it stops falling out again. It didn’t work for me.”
  — Dr. DeLoughery

4. Counseling Patients—Diet Myths & Realities

[28:17–32:26]

• Heme iron (animal sources) is best absorbed; plant (non-heme) iron, e.g., from spinach, is poorly absorbed and can even chelate iron due to oxalates.

• Eating steak isn’t enough for those already iron-deficient.

  “If somebody’s iron deficient, just eating steak three times a day is not going to get them back up...they’re going to need supplementation.”
  — [32:15]

5. Oral Iron Supplementation—Modern Best Practices

[33:27]

• Once daily dosing (not TID)! Higher frequency increases hepcidin, blocking absorption.

• With or without food? With food is fine for patient comfort and actual intake; “meaty” foods double iron absorption.

• Vitamin C with iron helps (especially to counteract dietary inhibitors).

• Avoid tea/coffee within an hour of iron—tannins drastically reduce absorption, not caffeine.

• For adherence, daily or three-times-weekly (e.g., M/W/F) is fine.

  “Once a day at most...People say take it on empty stomach - theoretically absorption may be better. People really don't like things on empty stomach.”
  — [33:27]

  “I’ve always wanted to actually make an iron pill wrapped in bacon...call it iron in a blanket.”
  — [28:17]

Every Other Day Dosing Controversy

[37:09]

• Every other day can improve absorption, but total iron repletion at 90 days is similar or slightly slower than daily dosing.
• GI side effects less common with every other day; overall, patient preference/tolerance guides choice.

6. IV Iron—When and How

Indications:

• Failure/intolerance to oral iron (no need to try endless oral formulations)
• High pretest probability of non-absorption (bariatric surgery, IBD, ongoing bleeding, severe deficiency)
  [48:10–49:19]

Dosing/Prep Selection:
[50:36–54:30]

• Multi-dose iron salts (iron sucrose, ferrous gluconate): practical downfalls, adherence issues.

• Preferred:

  • Low Molecular Weight Iron Dextran: Single 1000mg dose, safe & well-tolerated.
  • Ferumoxytol: 510mg x2 a week apart (off-label, single 1020mg dose works but not always insurance-covered).
  • Ferric Derisomaltose: Fast, single dose, but more expensive.

• Ferric Carboxymaltose: Watch for significant hypophosphatemia; avoid unless necessary.

  “Single dose iron...One stop shopping, and boom, the patient’s repleted.”
  — Dr. DeLoughery [51:28]

IV Iron Safety, Side Effects, and Counseling

[56:48–57:42]

• Infusion reactions (not true allergy) occur 1–4% of the time and are minor; anaphylaxis is exceedingly rare.

• No good evidence that IV iron increases infection in most settings.

  “True, severe anaphylaxis, very, very rare – like 1 in 15,000. And so it’s a very safe product to give.”
  — [57:11]

7. Population Pearls

• Premenopausal women: Take a menstrual history—heavy periods underrecognized as a cause; GI workup unnecessary unless over 40 or with risk factors.

  “You gotta take a menstrual history...that can really pay off.”
  — [44:35]

• Celiac workup: Always in men, and low threshold in women with unexplained anemia or GI symptoms.
• Unexplained iron deficiency: 20–30% of cases, extensive workup remains “negative”—reassure, monitor, treat supportively.

8. Monitoring & Follow-Up

[58:41–60:46]

• For oral iron: Check CBC at 2 weeks, expect 1g/dL rise in hemoglobin; monitor ferritin at 3 months, aiming >50 (or higher with ongoing symptoms).
• For IV iron: Check ferritin at 4–6 weeks (earlier = artificially high). Repeat as needed; expect ferritins in 200–300s after repletion, not a toxicity sign.

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Notable Quotes (/ Memorable Moments)

• On public speaking:

  “If you study, you actually know more than anybody else in the audience about it because it's fresh on your mind.”
  — Dr. DeLoughery [05:53]

• On heavy periods:

  “Average American woman needs 2.4 to 3.54 mg of iron a day to keep up with menstrual losses...and average diet intake is 1.8 mg!”
  — [44:35]

• On iron-rich foods:

  “Moose actually has the highest amount of iron in it.”
  — [29:54]

• On why spinach is not the answer:

  “Spinach is a not that great a source of iron, and it hurts patients...it actually chelates iron.”
  — [32:26]

• On surprising ferritin cutoffs:

  “Ferritin of 13 is not normal in any situation. Maybe for other forms of life, but not in humans.”
  — [68:59]

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Timestamps for Major Segments

• [09:36] Initial anemia assessment, case intro, CBC review
• [13:42] Systematic CBC reading, thalassemia/iron deficiency trick
• [19:21] Iron studies: Ferritin vs. TIBC/Transferrin saturation
• [21:04] Setting ferritin cutoffs & the pitfalls of population reference ranges
• [27:23] Higher ferritin targets for restless legs/alopecia
• [28:17] Dietary pearls & myths (heme vs. non-heme iron, spinach myth)
• [33:27] Oral iron dosing, hepcidin, food/vitamin C/tea tips
• [37:09] Once daily vs. every other day iron dosing controversy
• [48:10] When to move to IV iron
• [50:36] IV iron products—dosing, pros/cons, hypophosphatemia warning
• [56:48] Safety of IV iron, reactions, counseling on side effects
• [58:41] Monitoring response, CBC/ferritin follow-up
• [68:59] Take-home points

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Take Home Points (Dr. Tom DeLoughery) [68:59]

• Iron deficiency is common—define it physiologically, not statistically. For ferritin, use 30 (minimum) or 50 (symptomatic) as your cutoff, not lab “normals”.
• In women, take a menstrual history. It’s key and too often missed.
• Prescribe iron once a day at most; give with food/meat for tolerance and absorption.
• Don’t hesitate to move to IV iron—don’t “torture” patients with endless pill trials.
• Ferritin in the 200–300s post IV iron is okay—don’t sweat it.
• IV iron is safe—infusion reactions are rare and usually minor.

“Iron deficiency is really common… and we need to have a physiologic approach to lab values. 30, 50 ferritin cutoff, that’s what you got to keep in your mind. Ferritin of 13 is not normal in any situation… Iron once a day at most… and don’t be afraid to use IV iron.”
— Dr. DeLoughery [68:59]

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For further learning, see Bethany Samuelson Bannow’s episode on high menstrual bleeding and Dr. Michael Auerbach on IV iron (referenced by the hosts).

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Summary prepared for those seeking a comprehensive, practical update on iron deficiency anemia—and a few laughs.

Transcript

[Announcer]

Hey, before we get to the show, I wanted to remind you to check out our [e-mail] curbsiders. If you haven't signed up yet, sign up now to get ad free episodes, twice monthly, bonus episodes, and a whole bunch of other cool [e-mail] curbsiders.

[Dr. Matthew Frank Watto]

You know, Paul, I was helping my son with his math homework tonight and I realized something. The difference between a numerator and and a denominator is a short line. But only a fraction of people will understand that.

[Dr. Paul Nelson Williams]

So just a peek behind the curtain to our listeners. We spent a good amount of time trying to find a pun before actually starting the show and that was the one that Matt opted for.

[Dr. Matthew Frank Watto]

All right, one last one. Actually, I can't remember which ones I've done and which ones I haven't. Now forget it. Let's just get to the show.

[Dr. Paul Nelson Williams]

The Curbsiders podcast is for entertainment, education and information purposes only. And the topics discussed should not be.

[Dr. Tom DeLaure]

Used solely to diagnose, treat, cure or.

[Dr. Paul Nelson Williams]

Prevent any diseases or conditions. Furthermore, the views and statements expressed on this podcast are solely those of those and should not be interpreted to reflect official policy or position of any entity aside from possibly cash, like more responsible.

[Dr. Tom DeLaure]

And affiliate outreach programs, if indeed there are any. In fact, there are none.

[Dr. Paul Nelson Williams]

Pretty much, we aren't responsible. If you screw up, you should always do your own homework and let us know when we're wrong.

[Dr. Matthew Frank Watto]

Welcome back to the curbsiders. I'm Dr. Matthew Frank Watto, here with my great friend and America's primary care physician, Dr. Paul Nelson Williams. Hi Paul.

[Dr. Paul Nelson Williams]

Hi Matt. How are you? Happy New Year.

[Dr. Matthew Frank Watto]

Happy New Year. This is our first episode back in 2025 and what a great way to start with returning guests Dr. Tom DeLaure and Paul. We're talking about anemia and specifically iron deficiency anemia, which is extremely common. But there's a lot to be learned. Here are our guest has some fantastic pearls.

[Announcer]

Paul, before we introduce our co host.

[Dr. Matthew Frank Watto]

And tell the audience more about our guest, what is it that we do on the show? Because it's been a long time and I don't remember.

[Dr. Paul Nelson Williams]

Yeah, it's been a minute back from the break and we are still the internal medicine podcast. We still use expert interviews to bring you clinical pearls and practice changing knowledge. And as you alluded to, we are joined by super producer, especially this particular episode and our co host for this episode as well, the great Dr. Sai Achi. Sai, how are you?

[Dr. Sai Achi]

I'm good, how are you? Happy New Year.

[Dr. Paul Nelson Williams]

Well, thank you for asking. Happy New Year.

[Announcer]

Sai, would you please do us the.

[Dr. Matthew Frank Watto]

Honors and tell us about our guest and maybe just a couple things we talked about on the episode.

[Dr. Sai Achi]

Yeah, of course. So we have a fantastic conversation with our guest, Dr. Tom Delaure. He's a hematologist at the Oregon Health and Science University. He loves his job, especially teaching any and all learners. He's interested in all things classical hematology, especially iron deficiency. Plus, he's very active in teaching wilderness medicine. He enjoys reading, running, and trying out new recipes. His one oddity is that he's been to 43 Bob Dylan concerts in six countries. Dr. DeLaurie teaches us the workings of iron deficiency anemia, how to go from creating a roadmap on the different types and differentials in anemia to diagnosing and coming up with treatment options for our patients. So without further ado, let's get to it.

[Dr. Matthew Frank Watto]

And I would just say his one oddity. I don't. I would question that. I mean that lovingly, Tom. I mean that lovingly.

[Dr. Paul Nelson Williams]

He would agree. I was going to make the same comment.

[Dr. Matthew Frank Watto]

He reveals during the episode that he had ten bone marrow biopsies. And I asked him during a break. He said it was because his professor at the time was paying $75 a pop for bone marrow biopsies.

[Dr. Paul Nelson Williams]

Yeah, that was the caveat. But I did get paid for them because that makes it less weird.

[Dr. Matthew Frank Watto]

All right, a reminder that this and most episodes are available for CME credit for all health professionals through VCU Health at curbsiders.vcuhealth.org well, Tom, thank you for joining us on the show again. It's been a while since you've been here, so. Yeah, maybe you've picked up some new hobbies or interests. Tell the audience. I think last time you told us that a bat bit you and you had to get rabies shots, but what are you up to these days?

[Dr. Tom DeLaure]

That's great. Well, my hobbies are still. I run. I run a lot, actually. I had a hip replacement over a year ago, and I'm back to running five miles a day. My goal is to wear out that hip like I did my old one. And then fortunately, I did not get a DVT during the surgery. That would have been so embarrassing. But I flown out and seen Gene Connors for that. Just to hide it. And then I'm also a very, very avid reader. I don't tend to watch tv. I read a lot, mainly nonfiction. I'm reading an interesting book about the Eastern front in World War I, which also tells you I'm really a nerd. That's by Nick Lloyd. But I'm actually dipping my toes into fiction. The recommendation of somebody I trust recommended some novels. I think the Wind Up Bird by Murakama. And that was actually a very interesting and fast read. You know, I'd previously said I wasn't going to read fiction until I got done with all nonfiction. But I'm making some exceptions now. That's basically what I do. I still run and read and just enjoy life. And I do a little baking on the side.

[Dr. Matthew Frank Watto]

Another guest with a lot of healthy hobbies, Paul. Like, sounds like very productive hobbies.

[Dr. Paul Nelson Williams]

Yeah, no, it's good because Tom got a hip replaced. He's running five miles a day. I haven't run in about the past month and a half just because it's cold and dark outside and I just don't feel like it, so. Good for you. This is inspiring. Maybe I'll just turn things around this year. So I guess we'll go with the old standby. Maybe I'll ask you if you have any meaningful advice that you've received or that you often give. It doesn't even necessarily have to be medical advice. We'll take any sort of broad life experiences.

[Dr. Tom DeLaure]

I think there's twofold advice. One, a lot of people, when it's really nervous when they speak, they speak before a crowd or something, they're really nervous. And something my mentor told me that I actually tell other people is if you study, read on it, you actually know more than anybody else in the audience about it because it's fresh on your mind. And I found that pretty useful. The other piece of advice I always carry around is when I was a resident at the va, I was, like, grumbling one day, mad at the VA file room. You kids don't know about that. And you know where they store the X rays. And the chief of medicine came up to me and goes, tom, if you go home and there's not one thing that happened to you that made you laugh and you're taking it all too seriously. And so I've always kind of remembered that.

[Dr. Matthew Frank Watto]

So.

[Dr. Tom DeLaure]

So that's my general wisdom. I like to spread.

[Dr. Matthew Frank Watto]

Yeah, Paul, we could, you and I. I'll speak for myself. I could use that advice. I should remember to laugh more often when.

[Dr. Paul Nelson Williams]

No, anyone who knows me knows I'm a laugh riot. So.

[Dr. Tom DeLaure]

Yeah, yeah, you know, something crazy, a totally insane pre op, you know, something like that. It's just sometimes you just gotta laugh.

[Dr. Matthew Frank Watto]

Yes. Okay. All right, we probably have time for one more question. Sai, anything you wanted to ask.

[Dr. Sai Achi]

What's been your favorite failure, and what did you learn from it?

[Dr. Tom DeLaure]

Well, that was great. Well, that was also when I was a resident and I really, really wanted to be chief resident. Retrospect, I don't know why. And I was turned down for it. And it was a very graceful way. The head of medicine called me up and goes, delauri, chief resident, not you, and hangs up.

[Dr. Matthew Frank Watto]

Oh, geez.

[Dr. Tom DeLaure]

Yeah, I kind of was crushed. But then I realized that actually, instead of being chief resident, I started my fellowship earlier, actually did extra research, and actually turned out just to be okay. And, you know, I'm a big fan of Kurt Vonnegut. He's my fellow Hoosier. I actually heard him speak when I was in med school, and he has a wonderful saying from Kat's Cradle. Unexpected trips are tap dancing lessons from God. Just means, you know, if something goes wrong, that actually sometimes doing something different, going down a different path, may turn out to be better. So that's. I've always kind of remembered that. The other great thing about not being chief resident is there's actually all the residents for years have a secret society called Almost Chief Resident of People who Get Turned down, which I think is most prestigious. Plus, I've complained about it endlessly for the past, you know, many decades. So it's giving me something to be bitter about. So all in all, it's actually a very fabulous thing that got turned down.

[Dr. Matthew Frank Watto]

I'm sure they regret not picking you, but we, you know, maybe you wouldn't be Bloodman on Twitter or whatever it's called nowadays. That's true, you know, if that hadn't happened, so.

[Dr. Tom DeLaure]

That's right. So like I said, unexpected trips.

[Dr. Matthew Frank Watto]

But that program director probably, you know, that sounds like some sort of HR violation nowadays, but, Paul, what do you think?

[Dr. Paul Nelson Williams]

I appreciate their forthrightness, actually, you know.

[Dr. Tom DeLaure]

Got the point across.

[Dr. Matthew Frank Watto]

All right, well, let's get to our first case from Cashlak Sai, would you do us the honors?

[Dr. Sai Achi]

Let's do it. So our first case is that of Ana Mia and her husband Byron. So they present to your clinic for a routine follow up. And as you're going through your review of symptoms, though Ana Mia seems to be doing okay. Byron endorses that he's feeling tired and cold. He thought that it was due to him picking up extra shifts in the grocery store's meat section. He denies any weight loss. And so you order some basic blood work and find that he has a hemoglobin of 12 grams per deciliter and an MCV of 64 TSH is normal and his electrolytes are stable. So how would you kind of go about approaching this patient and this case?

[Dr. Tom DeLaure]

Well, that's great. You know, obviously from the initial labs, I have some ideas, but when I see somebody's anemic and labs come back anemic, you know, certainly I realize obvious things like have you been bleeding, you know, blood in the stool, throwing up blood. Have you ever been anemic before? Anybody in your family ever been anemic? And again, it's a little bit interesting because, you know, we tend to see anemia much more in women than men, but those are basically sort of my guide approaches to that. And then one thing I also try to do is just, you know, if you had any stomach upset, diarrhea, you know, trying to tease out symptoms of celiac disease. So. So those are my basic approaches. So those would be the extra questions I would ask. You know, are there old labs I can flip through? You know, is there something new? Something old? But that would be my initial approach.

[Dr. Matthew Frank Watto]

Yeah. And so we, we usually do the Paul Williams method of ordering labs, which is just like, if you didn't like the labs the first time, you reorder them to see if you get an answer, you like, yes. But, you know, if I saw an MCV of 64, hemoglobin of 12 in a man, I would. I don't think we exactly gave you an age, but I would. I'd be suspicious that something else is going on. I probably would order more tests on that second round. But what else should we order with that?

[Dr. Tom DeLaure]

Well, you know, actually, if you order enough tests, the patient does become anemic, and then you solve the problem. But so my second line test, again, I'm a little biased by obviously, the mcv, the presentation. So my general approach, maybe pulling back a bit, is I still like getting every tick count on people. You know, people often get jaded because it's never usually wildly abnormal. But. But, you know, if the retic count is up, that's going to point me to amalysis, severe bleeding. And I think it definitely goes down a different pathway. So I like dividing things that way. And then given his low mcv, I know there's. There's only four things that cause a low mcv, and that is thalassemia, iron deficiency, anemia, chronic disease, and sideroblastic anemia, which is pretty unusual, inherited in an adult. And then it's rare for the anemia chronic disease, be below 70. So right now I've narrowed it down to iron deficiency thalassemia suspect. This is new. You know, if I found an old CBC with normal MCV narrows it down to iron deficiency. So I think for him I would be, probably would start with a fairly narrow workup of the re tick and getting a ferritin. Now there are some cute, what I call parlor tricks, you know, for thalassemia. Like, you know, you divide the MCV by the red cell number. If you have a lot of little red cells, it tends to be thalassemia, lesser red cells, it tends to be iron deficiency. But I still like getting the labs to confirm. But you know, it's always a fun trick for the house staff when you're in clinic with them. So in him, I think I would get ferritins right off the bat. Now what's interesting is I tend to get ferritins in everybody. Why? Because A, iron deficiency is really common depending on how you define it. B, although the MCV is great, you know, 50 to 60% of people with iron deficiency will have a normal or high MCV. And my course records an MCV of 126. And C, as we'll get into, iron deficiency can be a, you know, a sign of other pathology. So I tend to be fairly liberal in ordering that, but I think for this guy I would be a little bit more focused in my work. Again from that strong clue of the mcv.

[Dr. Matthew Frank Watto]

And I was mentioning to you off air that when I ask people, what do you look at when I ask trainees, a lot of them, what do you look at when you're trying to work up anemia? Because it reports so many numbers on the cbc, unless they've been taught a good systematic way, they're not sure where to look. So you mentioned a couple things so far. Obviously we're looking at hemoglobin and mcv. What else is useful there for them to look at when they're, when they're thinking about anemia?

[Dr. Tom DeLaure]

Yeah, I'm pretty narrow. So basically I look at the red cell count Collector said sometimes, especially with microcytosis, that can give you a hint. You know, people tend to be the hemoglobin, hematocrit camp using one or the other. I used to be team hematocrit, but you know, the newer CBCs measure the hemoglobin derive the hematocrit. So if you want to be technical about it, they. Hemoglobin may be the more accurate number, but one or the other and then the only indice I really look at is the mcv. The other others are there to take up space. And you know, supposedly if the MCH is high, that's occluded red. Serious spirocytosis. It's actually never worked out for me. So I try not to look at the other indices, but, you know, for a cbc, I'm fairly limited to that. That's what I looked at.

[Dr. Matthew Frank Watto]

And even RDW too. No, not looking at that.

[Dr. Tom DeLaure]

Yeah, I've never been a fan of the RDW because when you look at the literature, it's not super predictive for iron deficiency or anemia, chronic disease. So, you know, it's a great theory, but in practice I think it's not panned out that much. So I tend not to be a big fan of it. So like I said, I'm pretty restrictive at what I look at. I mean, if they adopted my view on the CBCs, we'd save so many trees and paper.

[Dr. Paul Nelson Williams]

Right, well, inpatient phone calls. What am I supposed to do with this mchc? Yeah, but my question for you is, you know, being team hemoglobin or team hematocrit, are there situations where there is discordance there where like one, like where they would you would expect, where like one is abnormal and one is not. Or I guess what, like, I guess what is the utility of thinking about one or the other and how do you look at those things?

[Dr. Tom DeLaure]

Oh, that is great. They usually, you know, about three to one, so they're pretty standard. Sometimes if you're really microcytic, really macrocytic, it can be off and there the hemoglobin actually tends to be a bit more accurate. So again, I think a lot of us, you know, grew up with rules about hematocrit, but probably, if you want to be precise, and I'm kind of shifting over that way, hemoglobin is the way to go.

[Dr. Matthew Frank Watto]

And I have not been using the mcv and the red cell count. Can you tell us that calculation that you did again and how that make your parlor trick for thalassemia?

[Dr. Tom DeLaure]

Yeah, so it's what you do is you take the mcv, divide it by the red cell count in millions. So if it's under 13, it tends more towards thalassemia because your red cell number will be pretty big. If it's over 13, it will tend to be more for iron deficiency. So in thalassemia you make a lot of little red cells. In iron deficiency you don't make a lot of little red cells. So sometimes I may see somebody with thalassemia with a hemoglobin of 10, but actually the red cell number is increased. So that's kind of my tip trick for thalassemia.

[Dr. Matthew Frank Watto]

Okay. All right.

[Dr. Tom DeLaure]

I think it's called the Metzler's Rule if I'm remembering right.

[Dr. Matthew Frank Watto]

Okay.

[Dr. Tom DeLaure]

But if not, we call it the Paul Williams Rule.

[Dr. Paul Nelson Williams]

So yeah, that one's taken.

[Announcer]

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[Dr. Matthew Frank Watto]

That's freed AI. So our second round test, we're getting a CBC, a retic count and a ferritin. And then what about the transferrin saturation and like T iron tibc, Are those also?

[Dr. Tom DeLaure]

That's a good question. You know, some. The purist will say you should do all three as part of iron studies. My issue has always been with tibc and iron saturation is it's not, you know, the utility of. It's limited in people. So let's say you're older, inflamed, you know, your iron is going to be down anyway with inflammation, anything else. And then ideally, when you're iron deficient, your tibc goes up, but that's a very negative acute phase reactant. If you actually just give somebody a dirty look, their tibc goes down. And so that's a pretty unusual finding. And so a lot of times it may not be as good. And the big confounder is the iron saturation's also down in inflammation. And so I sometimes get it to get myself out of situations where. But, you know, there's studies done at Garnt Guide. I mean, it's over 30 years old, but still, the classic paper really said the one test that is most predictive is the serum ferritin. So I just tend to go with that. If it's borderline, there's element of inflammation asap, sometimes can help you. But I tend to be a purist just about getting the ferritin. You know, if I'm screening for hemochromatosis, I get an iron saturation.

[Dr. Matthew Frank Watto]

And then we're mostly taught ferritin. 15 to 30 or more is normal. Right. And a lot of the papers that I was reading to prepare for this are now setting the ferritin higher. So can you talk a little bit about that?

[Dr. Tom DeLaure]

Yes. That's been, I think, a big and important realization. So how labs usually do a range of normal or. Now they're called reference ranges. They'll margin like 100 medical students, 100 men, 100 women do ferritins. Guys, that's probably okay for we're rarely iron deficient. But you know, we know now, especially from the work of Angela Wayand and other people, that the instance of iron deficiency is really high in women. And there's actually a classic series about four studies of doing bone marrows in young women. And up to 50% or more had negative, had no iron stores. So iron deficiency is very, very common. Now the issue is you have a population, let's say, who's half iron deficient. You do your statistics and you're only going to say, hey, the lowest 2.5% is abnormal. Your ferritin is going to be wrongly very low. And so we need to move away from population based data to more physiologic data. And the analogy I use is cholesterol. Like when I was an intern, actually still in my original Washington manual, you know, normal for cholesterol is like 350 because that was 2.5%. And obviously we know now physiologically it should be a lot lower, I think like 10 now. But. And that's the same thing with ferritin is. And so where is the best cutoff is under discussion for a healthy person. Probably 30 is the best sensitivity and specificity for negative iron stores. What's interesting though is there's two studies that show that if you're fatigued, the cutoff ferritin for feeling better is 50 with oral iron. And when your ferritin falls below 50, there's several studies to show your gut absorbs more iron. Sort of like maybe that's a physiologic threshold. And if you do huge population studies of ferritins versus blood counts, actually very subtly, the MCV falls, you start to see the changes of iron deficiency at a ferritin of 50. So I personally use a ferritin of 50. There's a big movement at least to get it up to 30. There's a campaign going on in Canada called raise the bar. To get it up there. You get iron fortified, maple syrup or something and then. And that's up there. So it was interesting. One of my colleagues did an informal study of just having her daughter call 30 labs in Northwest. And the lower limit of ferritin ranged anywhere from five, you know, to a couple labs that were 30 or 50. So I think this is a case where you have my permission to ignore the lab values and you know, carry number of 30 or 50, whichever one you're happy with. Certainly 50 for patients complaining of fatigue or other things. Now the other situation, the ferritin gets thrown off is Inflammation. We're always taught ferritin's acute phase reactant. You know, it's just. And there's a subtlety here with that, and that is molecularly, your body needs iron to make ferritin. And so what happens is, if you have no iron, the MRNA of your ferritin doesn't get translated into protein. And so if you're iron deficient, you could be on fire, have TB and endocarditis, and your ferritin's not gonna get above 100 or so. And again, Gordon Guyett did this. A lot of studies, and maybe it's still a little wobble rumor out there, but if somebody's ferritin 600, they are not iron deficient, because you need iron to make the ferritin protein. So the ferritin is not perfect, but it's going to be the one test that's going to allow you to more accurately classify people if they're iron deficient or not. The other thing is, ferritin should go up as you age. You know, we guys, you know, steak kegers, things like that, we pile up iron. Women, postmenopausal, pile up iron. So a rule of thumb, which, to be honest, I've never statistically proven, but your ferritin probably should be higher than your age. There are studies of doing marrows in people over the age of 65, and if they had ferritins under 50, it was negative. Now, I always get some wise guy go, well, if your patient's 102 and their ferritin's 100 anyway.

[Dr. Paul Nelson Williams]

But if your patient's 102, why are you checking your ferritin?

[Dr. Tom DeLaure]

Yeah, I know, I know, I know. They want to keep fighting, so. So there's things like that. But in general, you know, if Grandma Perkins is 82 years old, and that's my standard old person name, I'm going to run to somebody named Grandma Perkins, and they're going to be really mad at me. And, you know, her ferritin's 20. No matter what the lab says, that's very abnormal. And Grandma needs to be worked up.

[Dr. Matthew Frank Watto]

I love it. Paul, this, this ferritin cutoff thing reminds me, like, we learned with liver enzymes, right? If you look at most labs, the AST ALT, they make the cutoff 40. But that's like a population study because they're. They're measuring, they're factoring in people that have inflamed livers, and actually they set the cutoff alt 20 for women and 30 for men. So we're with ferritin, instead of having that lower cutoff, it's dra. It's dragged down by all these iron deficient women where we're saying we should raise it and say that it should be 30, at least 30, probably 50, because once you replete them to 50, their fatigue gets better.

[Dr. Tom DeLaure]

Yeah.

[Dr. Matthew Frank Watto]

Okay.

[Dr. Paul Nelson Williams]

It feels haunting, though, like the vitamin D discussion too, where, Matt, when we were in training, we were just sort of picking these reference ranges that had no physiologic consequence. And so everyone would have been D deficient, even though there was no. Nothing was happening in the body at those levels. It's nice that we're actually thinking a little bit more physiologically, which is helpful, I think.

[Dr. Matthew Frank Watto]

I like it. Yeah, I like it.

[Announcer]

All right.

[Dr. Tom DeLaure]

Two other weird things to work in. There may have been time later, but I just thought of it is there's maybe a couple areas where the thresholds are higher. Actually, with restless leg syndrome, there's good data. You got get the ferritin above 75, if not 100. And interestingly, that's related to brain iron. And maybe you need higher ferritins to drive iron into your brain. And there is an association in the dermatologic literature of alopecia and ferritins, and that tends to start at 100. And what's interesting is I see that in my practice, my patient called me up and like, Dr. Lori, my hair is falling out. I know my ferritin's low and it's like 85. You give them iron, it stops falling out again. It didn't work for me. But that's something I keep in mind with hair loss.

[Dr. Matthew Frank Watto]

Paul, that might be my favorite pearl of the episode. It's gonna be hard to beat that one. That's fantastic.

[Dr. Paul Nelson Williams]

I don't just sell pick up iron.

[Dr. Matthew Frank Watto]

Yeah, yeah. Okay, well. Cause you do. I mean, you do get. I have so many people coming in worried about hair loss. And you check a ferritin and it's, you know, if it's somewhere between 30 and 100, I'm like, ah, it's. It's fine. But maybe trying to push it to 100 just to see if it helps. I don't see harm in that. Okay. All right, Sy, should we get to the next part of the case?

[Dr. Sai Achi]

Let's do it. So once the couple comes back to your office to follow up, Byron's surprised to hear that he has a low red blood cell count. He says that he eats liver and onions or a steak at least twice a week. So in this situation, how do you kind of break down or how do you approach and break down the concept of anemia for patients? And can you kind of elucidate about just foods?

[Dr. Tom DeLaure]

It's kind of ironic. I actually have a terrible diet, but I end up always giving a lot of dietary advice to patients. You know, it's great. They see me. You're walking to clinic carrying a bag of chips and a Diet Coke and, oh, you know, you need to be eating better. But so what I usually talk to patients about is, you know, you know that if you're anemic, usually you're not getting fuel to your bone marrow. And in many patients, like this patient, it's iron. So what I say is, you're not getting enough iron to your marrow, and that's why you're anemic. Surprisingly, I have a lot of patients go, why aren't you doing a bone marrow test? Which, I don't know. I've had 10 of them. I wouldn't do them unless I was getting paid for it. And so. Which I was getting paid for. And I always say, well, you know, we're pretty confident you're low on iron. You know, it'll go up with that. And so I relax about that. But, you know, the other thing they're always worried about is this, you know, leukemia or anything like that. And always reassure them that simply, you know, you need iron to make red cells. You know, in my day, there's that old patent medicine, geratol, and iron, poor blood, which hopefully is off the market. So I'm not getting in trouble for using a brand name. But so patients do understand that. So. So I do it with that. You know, sometimes where it gets more complex is hemolysis, where you're saying where your red cells are breaking down faster and, you know, maybe it's an immune attack. We got to figure out why. And that sometimes bothers people. So we walk, walk our way through that. Usually the one I find most confusing are the myelodysplastic syndrome, where there's a stem cell defect. And, yeah, basically analogy I use is like, your red cell factory is broken. You know, we need to think of things to support it or fix it. But usually I kind of explain it because the way I think about it as iron, B12 folate is fuel for your bone marrow. Erythropoietin, you know, turns on the on switch and things like that. So I think mechanical analogies, especially for guys, you know, working spark plugs, is really, really good. That's sort of the way I approach the anemia. Food's fascinating. Any type of meat has much better iron absorption. The iron in heme, heme iron that's found in meat, even fish or chicken, seems to have a separate receptor, seems to be much more effectively taken up. And inorganic iron that's found like in legumes, iron supplements, iron, you know, supplemented bread tends actually not to be as well absorbed, maybe 10% or a little bit less. And so ideally, you know, a meat rich diet can help. If you look at patients who eat a vegetarian or vegan diet, they're more likely to be iron deficient. So again we think of bloody red steak as having the most iron in it and indeed it does. I think moose actually has the highest amount of iron in it. But you know, even, even fish or chicken get some there. A little not as well known fact is actually meat protein helps iron absorption. So several studies done that if you take iron with like pork, fish, chicken, it doubles the absorption of the iron pill. So I have a lot of patients who aren't into bloody red meat but they eat fish, they eat chicken and I'll actually say take your iron pill with that, that will double the absorption. I've always wanted to actually make an iron pill wrapped in bacon. I was going to call it iron in a blanket and have that be my patented, patented medicine there. And so, but one thing is that if somebody's iron deficient, they're behind the eight ball and just eating steak three times a day is not going to get them back up and they're, they're going to need supplementation. So it's still 10 grams or so of iron, milligrams of iron in the steak and that's not gonna get em back up. Plus they'll mess up their cholesterol. So it may be helping for a steady state, but once you're down, you're gonna need some sort of therapy.

[Dr. Matthew Frank Watto]

Yeah, so I think that's the thing that's hard for patients to understand is that like they, they say, oh well, I'm iron deficient, I'm just gonna eat more steak and that should fix the problem.

[Dr. Tom DeLaure]

Yeah, that's an issue. Another thing is the spinach myth. You know, we all have these image maybe from Popeye shows and stuff that spinach is very iron rich. There's several issues with that. One, if you actually go back to the original Popeye, you actually eat spinach for vitamin A, nothing to do with iron. So you know, this is evidence based Popeye. Secondly, it turns out that spinach actually doesn't have that much iron. People speculate maybe it's a decimal misprint or something. And then thirdly, spinach has a lot of oxalate acid, which actually chelates iron. So spinach actually is a not that great a source of iron, and it hurts patients. I have patients come in. I don't know why I'm iron deficient. I'm drinking spinach smoothies every day, which sounds kind of like an abomination, but it's just not going to get them there.

[Dr. Paul Nelson Williams]

All right, Dom, so liver and onions alone won't do it. So this patient needs supplemental iron. So what is your approach to that? I feel like there's a million ways to do that. There's been a lot of hot discussion about how often and how to give it and when to give it and that kind of stuff. So how do you, as our expert, navigate oral iron supplementation?

[Dr. Tom DeLaure]

Well, this is what I do, so it must be the right way. No, but there are a variety of ways of giving iron. I think the biggest discovery is you don't do iron tid anymore once the days at most. Because let's say if I took an iron pill this morning, a protein called hepcidin rises in response to my body absorbing iron. And hepcidin blocks further iron absorption. And so it goes up and it nicely goes down. And interestingly, it actually takes about 48 hours to get back to normal. So clearly, once a day at most. There's a beautiful study in older patients years ago in the American Journal of Medicine where they gave people 15, 50, 50 tid of iron. Two months later, Ferritin rise was identical. And of course, the incidence of lock bowel and all sorts of GI issues was much higher. So once a day at most. So in general, I give iron once a day. People say take it on empty stomach. Again, theoretically, the absorption may be better. People really don't like things on empty stomach. So I actually will tell people it's okay to take it with food again, if they're any type of meat eater, even fish or chicken, that will double the absorption of the iron. And I think that raises the interesting vitamin C issue, which is still tremendously controversial. In fact, there was a meta analysis one of our recent journals that just was all over the map. But I think if you look at the vitamin C literature, several things stands out. One, vitamin C is really good at neutralizing things that inhibit iron absorption. So calcium especially. So fiber, calcium, things like that. So if somebody's eating a iron pill at their meal and, you know, maybe as a cheeseburger, as a source of their meat. Taking 500 units of vitamin C will neutralize the calcium effect and allow absorption. There are some nice studies and one recently published American journal, hematology, where they gave, you know, labeled iron and a cup of orange juice. And actually iron absorption significantly went up. And so I'm of the school that vitamin C does help iron absorption. Again, something I do, which is more, I would say, a delorean nuance is just because I've seen so many people not tolerate iron. Empty stomach, I tend to give it the little food. And again, meaty food is good. What brand of iron or what iron compound? Ferrous sulfate's the cheapest. It's 62 milligrams of iron. I tend to start with that. People don't tolerate it. Ferrous gluconate is about 30 milligrams of elemental iron. Little bit more expensive. I go with that. And then there are more proprietary irons like iron bis glycerate, that may be a little bit better tolerated. 22 milligrams a day. It's enough to get you by. Tends to be most expensive. So those are the oral irons I use. And I drive my wife nuts because we go shopping. I just go to the iron section of the supermarket and price things. But. But that. That's what I tend to do. The one thing I still avoid with iron is tea and coffee. They are powerful inhibitors of iron absorption, and so avoid tea or coffee an hour before and maybe about an hour after later. And I tell you, nobody in the Northwest likes to hear that. I told a medical student class that a few years ago, and they threw things at me. But they will decrease iron absorption 50 to 90%. Interestingly, it's nothing to do with the caffeine. It's actually the phenols, the tannins, the things they give tea and coffee. It's robust, wonderful flavor. And curiously, there's. The data's not great that even vitamin C will help. So a lot of my patients prefer to take it as an evening meal.

[Dr. Matthew Frank Watto]

Yeah.

[Dr. Tom DeLaure]

Now let's go to the once a day versus every other day controversy. So again, hepcidin stays up for 48 hours. So if I take an iron pill every day, my iron absorption of the iron pill is gonna decrease. And so I maybe absorb. You know, I'm making these numbers up, like 20%. If I take the iron every other day, when hepcidin wears off, I'm gonna absorb more iron from each iron pill. But the big question is, overall, what's going to be your total iron absorption? So my best take on the data from a recent study is that if you take one iron pill a day, you're going to replete a little bit faster at 90 days than every other day, where it may take you up to 180. And so with everyday iron, you're going to replete maybe a little bit faster. The downside is you're going to get more GI issues. And what's interesting is this study also showed that GI toxicity was really reduced with every other day iron. So to me, it's dealer's choice. You know, I can't remember taking my pills once a day. Well, somebody remembered to take it every other day. I think that's an issue. Maybe three days a week's good enough. Monday, Wednesdays, Fridays. I tend to start with every day and then cut back if people aren't tolerating it. Other colleagues will start with every other day, but I think in the end it's about the same. So in general, I personally start with once a day. I'm a little bit, you know, off the guidelines in that I like to give it a little food and vitamin C. Cause I think that improves patient absorption and patient satisfaction with the therapy. And I do it. And in him, again, he's really anemic. I check his CBC in two weeks, if you're gonna respond to oral iron, his hemoglobin should go up by a point in two weeks. And so that's kind of my basic approach to iron pills.

[Dr. Matthew Frank Watto]

Yeah, I love that Paul made this observation, like, years ago. I think this might have been seven years ago, Paul, when the iron thing came out. Paul's like, patients have known this just intuitively. That's just the way they take it. None of them are taking it three times a day.

[Dr. Tom DeLaure]

Yeah.

[Dr. Paul Nelson Williams]

Which I. It's again, I. I feel like I'm aging us, Matt. But, like, it's, you know, again, when we were in training, it was like, if they're kind of anemic, it's twice a day. If they're really anemic, it's three times a day. And like. And if God. God help them, if they were actually adherent, they would never poop again.

[Dr. Tom DeLaure]

So it's. I know.

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[Dr. Matthew Frank Watto]

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[Dr. Matthew Frank Watto]

I guess the last question I wanted to ask you and maybe this a little bit of a variation for this case. So Byron, our patient, let's say that he had, he, he's a man. So to work up his iron deficiency. He doesn't have celiac and we haven't seen any overt bleeding. He has, he had a colonoscopy and he had an upper endoscopy. Let's say maybe he even had a small bowel capsule study. They didn't find anything. What, how do you handle this? How do you explain it to patients when they. I have a handful of patients that I've seen over the past few years with like unexplained iron deficiency.

[Dr. Tom DeLaure]

Tom, that's actually a very common issue. So if you look at the studies, even classic Rockney study from years ago in the journal of really iron deficient older patients, 20, 30%, the workup is negative. And you know that really frustrates patients. Doctor, you can't tell me what's going on. You're the great iron expert and you don't know what's going on. And when I tell people several things, I say one well, you know, you have nothing bad. So we ruled out the bad stuff. That's somewhat Satisfying B. We know still how to treat it. But there are patients that seem to defy workup. A small percentage. It's weird little things like I had a patient taking one Motrin a day that was actually enough. We stopped it, she stopped bleeding. You know, there's, there's the rarer things which usually your GI worker will catch, but, you know, it's unknown. Maybe they just have subtle bleeding every now and then that you're not catching. Maybe they actually have some defect of iron absorption. They actually somehow excrete it or lose it through the valve. You know, it's actually a big mystery. Every iron expert I've talked to has the same group of patients that they really can't figure out what's going on. And I think also just telling people that's reassuring. Like, no, this happens about 20% of my patients. The other thing I emphasize is nothing bad pops up in the future. It's not like, oh my goodness, they developed a, you know, rhabdoshwano oma that, you know, from that, you know, they just need iron every now and then. So it's sometimes frustrating. You know, sometimes if you work up, esoterica comes up. But in general they just get iron. So that, that's. I, I feel your pain. That's a very common thing in my practice.

[Dr. Paul Nelson Williams]

So I will say in my limited experience that that's the type of patient where I'm the one who's more worried about than the patient is like, I'm seeing like the MCV kind of up and down. They're, they're like mildly anemic that they don't feel it. I'm like, we have to find out why it's happening. And when we don't, they're like, all right, as long as it's nothing bad. You're like, okay, cool. Besides, I feel I get more frustrated often than the patients are, but maybe that's the way I'm framing it.

[Dr. Tom DeLaure]

Isn't there a Marvel character that's somehow Iron man that can suck iron out of people? Maybe that's what's going on.

[Dr. Paul Nelson Williams]

It's Magneto.

[Dr. Tom DeLaure]

Yeah, Magneto. Yeah. He's like they're riding the train with them and a little bit of their iron gets sucked out.

[Dr. Matthew Frank Watto]

Well, I think we should move on to our next case. So Sy, would you do the honors?

[Dr. Sai Achi]

Sounds good. So we have Ms. Ivy Irons. She's a 34 year old lady who's presenting for an annual physical. She says that she's been having some intentional weight loss and Feels great. Apart from the occasional fatigue, which she says is because she's in the process of defending her thesis and has some fatigue around her menses. So her hemoglobin is 11.5, MCV is 59, and platelets are 550. TSH and other labs are stable. So how does a script change now that we're dealing with anemia in women, especially menstruating women?

[Dr. Tom DeLaure]

Great. I think that's a very good question. So the big thing that you gotta talk to and work up is menstruation. Again, I cannot compare to friend of the show, Bethany Samuelson Bano, who did a thing on heavy menses many years ago, which is still an excellent thing I recommend to my students. But you gotta take a menstrual history and. And for us guys, that's always a disaster. But. But you gotta ask it. So that's something I ask in every visit. You know, how long are your periods? How heavy are they? Pads, tampons, used? You know, if you're having periods enough to make you iron deficient, you gotta think of a bleeding disorder. And it's really interesting. Women will not a lot of times bring that up. There's several studies that show that women with heavy symptoms of a menstrual period, 50% of it, never mentioned it to their doctor. So you gotta ask them. The other interesting thing is it can happen in any group. Again, we tend to think of women athletes as not having periods, scant periods, but actually 25% or so can actually have heavy menstrual bleeding. So to me, that's the big thing that needs to be asked. That can be something you can certainly intervene in with IUDs, menstrual control, things like that. My GYN colleagues and, you know, Bethany's much better at than me, but I think that's usually the number one, two and three issue that needs to be addressed. And, you know, that's a big dilemma. The average American woman needs about 2.4 to 3.54 milligrams of iron a day to keep up menstrual losses. And what's interesting is the average American diet, women intake and absorb about 1.8. So that's why we see so much iron deficiency. There's this huge imbalance. And again, if you're having heavier periods, it just makes things worse. So I think that's really the big thing there. You know, one thing we discuss is when do you do a GI workup? I almost never do it in a younger woman. It's a Menstrual history. I think the exception are obviously GI symptoms or if there's a family history of colon cancer, gotta think about pulling the switch or over the age of 40. But again, it's really important to take a menstrual history. Ask everybody with iron deficiency that. And that's often a very fruitful way of discovering the source and actually being able to do something about it besides give iron pills.

[Dr. Matthew Frank Watto]

Are you sending celiac in a lot of patients or just if they have like GI symptoms or you get.

[Dr. Tom DeLaure]

I do it in two situation, I do it in all guys. I do it if GI symptoms and you know, if somebody's making a second visit or it's just, it's just a funny story like, no, I haven't had periods and stuff. I'll send it. Because especially, you know, in certain populations, disease is very, very common. They can have really strange presentations or not unclassical one, like a friend of mine's daughter. Actually her only presentations was intractable hiccups. So you could see things like that. So I think that's been a pretty. And like I said, I usually pick up a couple cases a year in working up iron deficiency.

[Dr. Matthew Frank Watto]

Yeah. Okay. I have a pretty low threshold to order celiac testing myself. Okay. So with this patient, we talked a bunch about, you know, diet, we talked about oral iron. So let's say she comes back to the office, she. She tried the oral iron tablets. Her symptoms are the same from last time. Hemoglobin is 11.8. Just to remind you, it was 11.5 when we started. Her MCV is still low. It's in the 60s. So when is it time to reach for IV Iron?

[Dr. Tom DeLaure]

Right then and there. So I think about IV Iron and people don't respond. And I don't, you know, torture people with other iron formulations. If they're not going to respond to iron, they're not going to respond. I think also intolerance. And again, I'll sometimes see people like, well, I tried this iron. I tried it once a day. I tried it every other day. I stood on my head again. If somebody's really having GI symptoms, I just go to IV iron. Certainly if I have a high pretest probability, they're not going to respond. Like bariatric surgery or chronic bleeding like hht. I may think about it and a little bit different than actually a paper I'm an author on. But of the GI guidelines. I tend to give IV iron to all inflammatory bowel disease. There's evidence, even in mild anemia, it will cause GI upset, it may cause an adverse biome, it can be inflammatory so I tend to give it. But certainly somebody with bad inflammatory bowel disease, I go with IV iron right off the bat. So I think nowadays we have a pretty low threshold of going to IV iron either in people, you know, it's not going to respond or in people who aren't responding or having intolerable symptoms.

[Dr. Paul Nelson Williams]

And Tom is there, I feel like I know the answer to this but is there like a ferritin threshold that you think about as well as like if there's an extent of iron deficiency or like you know, I'm not even going to fuss around with pills. I'm just going to go straight to the IV iron ore that really depend on one patient presentation and acuity and tolerance.

[Dr. Tom DeLaure]

That's what I'll do. Like and I think tolerance of that. So you know, again if somebody's old like grandma comes in with a, you know, ferritin of 2, she's having chest pain, I'll probably go to IV Iron sooner just not to mess with that. But you know, if you came in, Your ferritin was 5, your matocrit was 22, but you're doing okay. I still may give iron pills a try. Some people would go straight to IV iron. I'd like to give oral iron a try. So I think it's more the gestalt of the situation.

[Dr. Matthew Frank Watto]

Now in places I've worked iron sucrose and what's the other one? I guess ferrous gluconate are the most common iron preps that I'm seeing and those are multi dose like iron sucrose. I think you can give 300 at a time at most. And the ferrous gluconate you can give like 250 or something. So yeah, can you talk a little bit about like the gold dose for IV iron and then what formulations are out there and maybe order them, like which ones do you like?

[Dr. Tom DeLaure]

So that's a great question. You know, one debate is how do you determine the dose? And you know there's like formulas and stuff out there. They, they may not be that accurate. We, we have actually a project we're working on to see if the formulas actually are predictive. But the other thing is a lot of iron, IV iron comes in fixed doses like a thousand milligrams. So in general most of us just give a thousand milligrams. And you're right, the iron sucrose gluconate, the preparations we call the iron Salts, you need multiple doses and the reason why is they have more labile iron in it. So if you try to give a higher dose at once, the patient's significantly going to have a higher rate of reactions. So you have to infuse it in painfully slowly or you do the multiple infusions. And we actually have a paper out that in pregnancy when women were given, you know, prescribed multiple doses of iron sucrose, a lot, a lot of them just didn't simply show up after the first dose. So so you know, patient has to drive, it's inconvenient, you got paid for chair time. Every infusion of iron has a risk of infection. So I'm really not a big fan of multi dose iron. And no iron product safer than the other. There's actually one iron product that for obscure reason may be a little bit unsafer if that's the right word. But I'm from Indiana. But in general we love single dose iron. So my go to has been low molecular weight iron dextran. You give it as a thousand, you run it in over an hour and boom, the patient's repleted. One stop shopping. And so that's kind of been our standard because it's usually the cheapest get short every now and then. There's the most experience with it, abundant data, pregnancy, other situations. So in general that's my go to dose. Formoxitol is an interesting iron that also doubles as an MRI contrast reagent and so kind of a curious thing there, but it's also very effective at iron repletion. Now it has a silly dosing of 510 milligrams given twice, separated by a week. We have a lot of data we publish. My good friend Michael Auerbach, another friend of the show, also has data a given 10, 20 once. Very effective, very safe. Somewhat insanely, insurance won't cover that even though it's actually cheaper and less chair time. But that's our healthcare system. But that's another one. Patients have to inform the radiologist that they're getting an MRI of it. There's a newer product on the market, ferridesrel maltose, which really strains my ability to pronounce. It's also a single dose iron and give it in 20 minutes. Not much experience with it because it tends to be much more expensive than the other iron products. So in general I like to go with lumaliquate iron dextrans. There's been issues with this. My second go to now is formoxitol. Again dairy's maltose tends to be a little bit more expensive. Now you notice I did not talk that much about ferric carboxy maltose. So that for years has been a very popular iron. It's a few oddities about it. One, the vial size is 750. So you can either give 750 or give 750 twice for 1500. Everywhere else in the world it's a thousand, but here it's not. I don't know why. It has this very curious side effect. It actually causes hypophosphatemia. About 50% of people will get phosphoruses below 2, 10% it will be severe and it is symptomatic. There was actually an elegant study in people with inflammatory bowel disease where that their fatigue response was blunted. If they're hypophosphatemic, that is the low phosphorus or making them fatigue, blending the goodness that IV iron cause. So a lot of us are really pulling back from that iron. If you do it, you gotta check a phosphorus before you give a second dose. Really don't give it a lot. And what's bizarre is just by the mechanism, which I can't remember, you know, I remember the coagulation cascade. I can't keep other things in my mind that actually if you give phosphorus you make things worse. So yeah, so it's an interesting side effect and a lot of us are really pulling back and there's more and more data. So I kind of keep that totally reserved. So what I tend to do, as I said, is my go to is low molecular iron dextran. It's good for you.

[Dr. Matthew Frank Watto]

Yeah. The, the mechanism of it. I have the figure in front of me because I was going to ask you about it and it's. So it inhibits the breakdown of FGF 23 and then with this increase in FGF 23 that does two things. There's more phosphate excreted from the urine and it actually decreases conversion of 25 hydroxy vitamin D to 1,25 hydroxy vitamin D. So you have less active vitamin D around and you have more urinary excretion and the phosphate goes down.

[Announcer]

Paul, what's scary about.

[Dr. Matthew Frank Watto]

I had never heard of this before. And what's scary about this, it says it can occur with like even up to after six months after they receive that. Oh my God, that iron formulation and that there's not really a known treatment. Like it just sounds miserable and the patients are symptomatic. It sounds really bad.

[Dr. Tom DeLaure]

Yeah, yeah. I've had a patient or two with it. And I just have, like, thrown up my hands, and I. Like I said, there's some rare times I use it, but I think all of us are really pulling back from using it.

[Dr. Matthew Frank Watto]

Yeah. Okay. So, you know, if. I guess if we're forced to use the iron salts, you know, that's kind of what we're forced to do. But if we have access to the low molecular weight iron, Dextran, that's a good one to go with. And then Ferumox at all, however you pronounce it, that one. We just have to let a radiologist know if they're gonna be having an MRI within a couple months of receiving it.

[Dr. Tom DeLaure]

Perfect. Yes.

[Dr. Matthew Frank Watto]

Okay. Paul or Sai. Any other questions about IV iron?

[Dr. Paul Nelson Williams]

No, that was really helpful, actually. Like, I. That's. Yeah. Cause you get the list that is like a mile long. And if you have the paper to fill out where you have all these options, you're like, I don't. I don't know, whatever makes them better. So this helps me narrow it down. So I appreciate it.

[Dr. Tom DeLaure]

I always agree. And, you know, a lot of patients are kind of scared. Like, oh, you know, my Uncle Joe got it. He dropped dead and things like that. And what I emphasize to patients is we actually, a few years ago, published our experience with 35,000 iron infusions. Yes. We give a lot of iron. And one thing is people can have minor reactions or, like, infusion reactions maybe 1 to 4% of the time. And, you know, it's kind of scary. They itch, their throat tights. They maybe get a little rash, but it's just nonspecific activation of complement. I tell people that it's not an allergy. It's infusion reaction. It will happen. We stop it. We wait. It will go away. And it most often does. You know, in the old days, people like, oh, my God, it's an allergy. You know, get the crash card. And it just made a terrifying experience. So I forewarned patients that will happen. Our protocols about watching it, you know, maybe one in 200 times, it's an upper reaction, like, hey, let's do something different, a different day. But true, severe anaphylaxis, very severe reactions are very, very rare. Like 1 in 15,000. And so it's a very safe product to give again. Some people have these funky things. They're forewarned. They can just ride it right through. So, like I said, and people respond, they think you're great because they feel better.

[Dr. Matthew Frank Watto]

Yeah, that was, you know, when we talked to Dr. Auerbach about this. I think that was what got people most excited about the IV iron is that he, he's saying, yeah, if I give somebody a thousand milligrams IV iron, even before their hemoglobin is better, they feel better. And, you know, so you're making someone feel better in an hour.

[Dr. Paul Nelson Williams]

Well, yeah, I think he was saying that this is like the pagofagio goes away, like during the infusion, which I think was just like, kind of mind blowing.

[Dr. Matthew Frank Watto]

Yeah.

[Dr. Paul Nelson Williams]

But I guess above and beyond asking if they're still chewing on ice or not, like, what does your laboratory follow up look like? Like, how often is it meaningful to actually repeat your iron, your ferritin level, or doing a repeat cbc? What is your, what is your follow up? And how do you know it sticks? And when is the right time to actually chase those things down?

[Dr. Tom DeLaure]

Yeah, I just give a patient a plate of ice. If they don't eat it, I'm satisfied. That's a great question. So with oral iron, I usually like to check within a couple of weeks the cbc, see if it's going up, and then to follow it. Usually three months is my magic time with oral iron to make sure the ferritin's at goal, getting the crit up again. I like ferritin's above 50 or higher and older people IV iron, there's a little uncertainty when to check. If you check it too soon, the IV iron cross reacts with the ferritin and that gets everybody excited. I personally check it in about a month to make sure it's gone above my threshold. And then I like doing about every three months or so. So my colleagues will check it at six weeks. You know, that's a little variable. What always gets people excited, especially in my women patients, is that, you know, if you're successful, the ferritin is going to be up to 200, 300. And insanely many labs that's above normal for women. And I get these calls or they have hemochromatosis, things like that. Like, no, I've treated successfully their iron deficiency. And so, you know, sometimes you get a whopper ferritin of that. You just, you just ride it out. But in general, I like to do it about a month later. You know, if it's not about 50, they need another dose of iron to fill up their tank. And the only exception I make is sometimes you run into somebody really iron bankrupt. You know, their maticrets 20, their ferritin's one. You know, your ferritin's being drawn out as you talk to them. I might check them in two weeks, if the ferritin's not up, then give another slug of iron. But most people about four to six weeks, I check then. I think it's key to kind of at least for a while, monitor iron on a regular basis to see if it's stable or you know, if they're going back down again so you can catch them before they get as sick again. You know, if they should have really ironed, bankrupt. You don't want that to happen again. So, you know, I'll have patients every day I look at scads of ferritins and you know, if they're below 50, boom, we press the button for more IV iron.

[Dr. Matthew Frank Watto]

Yeah. And I mean patients that have had a good experience with it in my, like in my panel, they're pretty, they are asking me, hey, I, I'm feeling like, I feel like we need to check my iron. I think I need IV iron again because patients like it, you know, because they can tell that it, it's benefiting them.

[Dr. Tom DeLaure]

So yeah, I think we all should get some after the show.

[Dr. Matthew Frank Watto]

Yeah, I mean, hey, at the after party, you know, I'm down if any of you guys know how to start an iv. I haven't started an IV in such a long time. Okay, so we've, we treated Ms. Ivy. We treated her, let's say we with low molecular weight iron, Dextran. She feels great, she loves us. I think we have one last case to quickly go through so Sai, would you like to do the honors?

[Dr. Sai Achi]

Yes, let's do it. So we have Ms. Malik, Nancy. So she's a 55 year old lady who's coming in to see you as a primary care after her former PCP moved away. She's been having some fatigue lately and she attributes it to her age catching up to her. She says that in regards to her weight loss, she doesn't feel like eating much. However has been doing okay. You observe from her prior records that she's had a 10 pound weight loss since her last visit to her old PCP. Her labs are showing a hemoglobin of 8 with an MCV of 66. She's on iron tablets currently and she just got her age related cancer screening but didn't get a chance to share the results with her former pcp. And as you see her reports, there appears to be a lung nodule that has cancerous features. So in this case, how are we approaching her anemia?

[Dr. Tom DeLaure]

Yeah. So this case she's still probably iron Deficient. But obviously we have to be worried. There's a strong element of the anemia, inflammation, anemia, chronic disease. And so there is the disease again with our friend. Hepcidin is dramatically elevated. Hepcidin's blocking iron absorption. It's blocking iron being released from the liver. So the red cells are undergoing dual damage. They're not getting iron, cause they're iron deficient. And, and any iron that's there is being locked up. So the several implications, one is oral iron is just not going to work. You're not going to absorb it. So we see that a lot. Renal disease, we see it heart failure, we see an inflammation. So probably much more likely to pull the trigger on IV iron in this situation. And so, you know, she's somebody who probably I would just go with IV iron first because especially she's one of our tablets and snot working. So I think that that would be a key case. So again, I think if, you know, obviously because of the lung cancer, she needs C hemoc and you know, you're unable to do it, they can do the IV iron. But I think in that, in that case, because the underlying inflammation, that oral iron is not going to get anywhere, it's okay to do it and you know, it's not going to feed the tumor or do anything like that. It's just going to make the anemia better. You know, the other thing that runs up is there's always this thought that like, IV iron will cause infections. You know, well, bacteria need to iron to. You're given a lot. You know, it's like marigold Gro for infections. And I think that's been pretty much dismissed. The pivotal trial in people with renal disease who got, you know, lots of IV iron, there's no increased risk of infection. You know, most infections with iron are actually related to the lines and stuff that get infected from giving the iron. And, you know, it's free iron that does it. And you got to remember, free iron, even when you give IV iron, it's not there. The iron you give is in a matrix of, let's say, low molecular dextran. It gets absorbed by your body, it's put into storage, and so there's very little free iron there. So even if you think about theoretically, there's not that much for the bacteria to eat. So I, I personally haven't done it. You know, somebody's in septic shock, I tend not to give IV iron. But other than that, you know, somebody has a stable controlled infection, you know, I have no Issues with IV iron. But again, this patient, because of her cancer inflammation, it's not going to get absorbed. I think what's gonna be interesting in the future, just for people, it's straightforward anemia, chronic disease, There is interest in blockers of hepcidin and, you know, will that make people less anemic? Will we need less EPO in people with renal disease? I think that's gonna be the exciting future. What's curious about hepcidin is it's a funny protein. It's a very tight ball of amino acids. It's actually very difficult to make antibodies to. So we actually don't have great laboratory assays, which is bitterly disappointing. Disappointing because, you know, anemia, chronic disease is still a diagnosis of exclusion. Your iron stores are good. There's nothing else going on. It'd be great to have a diagnostic test like, oh, your hepcidin's 30 bazillion. So maybe one day in the future. But this is again, a patient that I would strongly think about just going straight to IV iron.

[Dr. Paul Nelson Williams]

And Todd, I guess a couple of the places that I've worked, it's. They develop protocols so that you can get IV iron infusions without having to drag hematologists into the mix. Like, I need to show to an infusion center. You fill out the orders, the magic happens. Who, who are the patients? I mean, obviously this patient needs to see an oncologist, but who, who are the patients otherwise with anemia that you would want to see that are that, like, who are the referrals that we should be sending your way when it's just not quite as straightforward?

[Dr. Tom DeLaure]

Yeah, that is great. So I would say somebody probably gets repeated IV iron. That's probably somebody I should see. You know, I may not offer anything better, but probably should see, make sure they're not doing anything. You know, there's more complexity to it. Like, the other accounts are wonky, things like that I should see. But in general, you know, a lot of my primary care colleagues, especially around the rural areas of the state, do a wonderful job at taking care of iv, you know, IV iron deficiencies. So I think, you know, repeated something unusual or it's like, boy, you know, it's like, you know, maybe the first case, a young guy, a young man with no obvious cause getting it. I think it's worth, you know, for a hematologist, given the once over, but, you know, somebody pretty straightforward iron deficiency, if you're comfortable with it, got good protocols. That's clearly a primary care issue.

[Dr. Matthew Frank Watto]

Well, that's great. Paul or Sy, any other questions before we get to take home points?

[Dr. Sai Achi]

I think one question I had is if you're looking at any of these infusion reactions, is the protocol to just slow the rate down or do you kind of pause the infusion and then start back once they kind of get over those minor symptoms?

[Dr. Tom DeLaure]

Great. That's what we do. So we tend to do is stop the infusion, wait about 15 minutes, and then restart. There's a wonderful paper by, I believe it's called Remton. Hopefully it'll be in the show notes that has a very nice protocol for minor, major and moderate reactions. But usually we just stop and wait. One thing we avoid is I can't even think of the trade, the real name of it but Benadryl. And it's because that. That has been shown to actually make infusion reactions worse. Also, like, oh, my mouth's really dry, or my heart's racing. So it's a drug I don't even, like, I can't remember how to pronounce the diphenhydramine. There you go. That's why we have the experts here. And so I avoid that like the plague. And especially should not be part of any iron infusion reaction protocol. But in general, we stop, reassure, go on, go on our way.

[Dr. Paul Nelson Williams]

I feel like we're down to, like, one indication for diphenhydramine now. Like, I don't think there's a whole lot else to really use it for.

[Dr. Tom DeLaure]

Yeah, yeah, yeah.

[Dr. Matthew Frank Watto]

I thought that was interesting. You know, one of the articles that you had written, you were just talking about kind of coaching patients ahead of time, how you coach them. Like, you might get these minor reactions if you do, that's to be expected. We stop the infusion, we kind of hanger. We. We wait. And then just mentioning that the diphenhydramine can actually, like, cause, like, flushing or tachycardia from the anticholinergic effects, and that can make the reaction worse or seem worse than it is. So interesting.

[Dr. Tom DeLaure]

Yeah, so I avoid it, like, so I haven't even learned to pronounce the name.

[Dr. Matthew Frank Watto]

All right, well, let's get to take home points. Tom, this has been fantastic. Very entertaining as always. Lots of pearls here and things that are practice changing for me. So thank you so much. But what. What do you want the audience to remember from this discussion?

[Dr. Tom DeLaure]

So I. I would say several things. One, iron deficiency is really common. Again, how you define it can be 50 to 70% of premenopausal women. I just reviewed a paper 50% in women athletes, it's really common and we need to have a physiologic approach to lab values. 30, 50 ferritin cutoff. That's, that's what you got to keep in your mind. You know, a ferritin of 13 is not normal in any situation. Maybe for other forms of life, but not in humans. Secondly, in women, it's really key to take a menstrual history. You know, it's something many people may not be comfortable with, but that can really pay off. Thirdly, iron once a day at most. Again, personal deloreanism. I like to get with food and meat and then don't be afraid to use IV iron. Don't torture people with oral iron if it's not working. IV iron is our friend.

[Dr. Paul Nelson Williams]

This has been another episode of the Curbsiders bringing you a little knowledge food for your brain hole.

[Dr. Sai Achi]

Yummy.

[Dr. Tom DeLaure]

Still hungry for more?

[Dr. Paul Nelson Williams]

Join our Patreon and get all of our episodes ad free, plus twice monthly bonus episodes at patreon patreon.com curbsiders. You can find our show notes at the curbsiders.com and while you're there, sign up for our mailing list to get our weekly show notes in your inbox. This includes our Curbsiders Digest, which recaps the latest practice, changing articles, guidelines and news in internal medicine.

[Dr. Matthew Frank Watto]

And we're committed to high value practice changing knowledge and we want your feedback. So please email [e-mail] it also helps us a lot if you give us five stars or like subscribe, whatever. And a reminder that this and most episodes are available for CME Credit for all healthcare professionals through VCU Health at curbsiders.vcuhealth.org I wanted to give a special thanks to our writer and producer for this episode, Dr. Sai Achi, and to our whole Curbsiders team. Our technical production is done by Podpaste. Elizabeth Frodo does our social media. Jen Watto runs our Patreon. Chris the Chewman Chu moderates our Discord. Stuart Brigham composed our theme music and with all that, until next time, I've been Dr. Matthew Frank Waddo.

[Dr. Paul Nelson Williams]

I'm Cy Achi and as always, I remain Dr. Paul Nelson Williams. Thank you and goodbye.